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姜黄素处理人肝癌 Hep 3B 细胞后蛋白激酶 C 同工型的激酶基因表达和亚细胞蛋白表达模式。

Kinase gene expression and subcellular protein expression pattern of protein kinase C isoforms in curcumin-treated human hepatocellular carcinoma Hep 3B cells.

机构信息

Department of Food Nutrition, Chung Hwa University of Medical Technology, No. 89, Wen-Hwa 1st Street, Jen-Te, Tainan, 717, Taiwan.

出版信息

Plant Foods Hum Nutr. 2011 Jun;66(2):136-42. doi: 10.1007/s11130-011-0228-2.

Abstract

Curcumin, a yellow component of turmeric or curry powder, has been demonstrated to exhibit anti-carcinogenic effects in vitro, in vivo, and in human clinical trials. One of its molecular targets is protein kinase C (PKC) which has been reported to play essential roles in apoptosis, cell proliferation, and carcinogenesis. In this study, PKC mRNA expression was significantly inhibited in curcumin-treated human hepatocellular carcinoma (HCC) Hep 3B cells identified using a kinase cDNA microarray. Furthermore, curcumin decreased total protein expression of all PKCs in a time-related manner by immunoblotting of whole cell lysates, nuclear, membrane, and cytosolic fractions. In cytosolic fraction, the expression of PKC-α was totally inhibited by curcumin. In contrast, the expression levels of PKC-ζ and -μ were dramatically increased. Increases in expression of PKC-δ and PKC-ζ in the membrane and nucleus, and PKC-ι in the membrane were detected. In summary, the changes in expression and distribution of subcellular PKC isoforms in curcumin-treated Hep 3B cells suggest possible PKC-associated anti-tumor mechanisms of curcumin and provide alternative therapies for human HCC.

摘要

姜黄素是姜黄或咖喱粉中的一种黄色成分,已被证明在体外、体内和人体临床试验中具有抗癌作用。其分子靶标之一是蛋白激酶 C(PKC),据报道,PKC 在细胞凋亡、细胞增殖和癌变中发挥重要作用。在这项研究中,使用激酶 cDNA 微阵列鉴定出姜黄素处理的人肝癌(HCC)Hep 3B 细胞中 PKC mRNA 表达明显受到抑制。此外,姜黄素通过全细胞裂解物、核、膜和胞质部分的免疫印迹,以时间相关的方式降低所有 PKC 的总蛋白表达。在胞质部分,姜黄素完全抑制了 PKC-α的表达。相比之下,PKC-ζ 和 -μ 的表达水平显著增加。在膜和核中检测到 PKC-δ 和 PKC-ζ 的表达水平增加,以及在膜中检测到 PKC-ι 的表达水平增加。总之,姜黄素处理的 Hep 3B 细胞中细胞内 PKC 同工型表达和分布的变化表明姜黄素可能具有与 PKC 相关的抗肿瘤机制,并为人类 HCC 提供了替代治疗方法。

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